Prediction of cancer neoepitopes needs new rules

Brennick, Cory A.; George, Mariam M.; Srivastava, Pramod K.; Karandikar, Sukrut Hemant

doi:10.1016/j.smim.2020.101387

Cited by 23 publications

(29 citation statements)

References 67 publications

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“…The low-affinity of TRMNs for MHC I may influence the phenotypes of T cells engaged by pMHC I complexes: (a) During cross-presentation, fewer APCs present the low affinity peptide (as compared to a high affinity peptide), causing T cells to receive a signal through the TCR less frequently, and (b) on an APC that presents the low affinity peptide, there will be fewer pMHCs on the cell surface that contain this peptide, resulting in a relatively lower avidity for T cell recognizing this pMHC on this cell. Both consequences will lead to a less exhausted T cell phenotype (29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

An unbiased approach to defining bona fide cancer neoepitopes that elicit immune-mediated cancer rejection

Brennick¹,

George²,

Moussa³

et al. 2021

Journal of Clinical Investigation

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Section: Discussionmentioning

confidence: 99%

An unbiased approach to defining bona fide cancer neoepitopes that elicit immune-mediated cancer rejection

Brennick¹,

George²,

Moussa³

et al. 2021

Journal of Clinical Investigation

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“…Despite their clinical success, objective response rates are not yet satisfactory (20-30% for many types of cancer) (37), highlighting the need to combine ICI with approaches that aim to generate and sustain speci c antitumour CD8+ T cells (e.g., therapeutic cancer vaccines) (38,39). In this scenario, to design effective tumour rejection and protection strategies, the reliable identi cation of tumour peptides binding to HLA-I has become a hot topic (6,40,41). The direct identi cation of the peptides from the HLA-I complex still represents the best-established and the most widely used method for their identi cation (42).…”

Section: Discussionmentioning

confidence: 99%

PeptiCHIP: a novel microfluidic-based chip platform for tumour antigen landscape identification

Feola

Haapala

Peltonen

et al. 2021

Preprint

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Identification of HLA class I ligands from the tumour surface (ligandome or immunopeptidome) is essential for designing T-cell mediated cancer therapeutic approaches. However, the sensitivity of the process for isolating MHC-I restricted tumor-specific peptides has been the major limiting factor for reliable tumor antigen characterization, making clear the need for technical improvement. Here, we describe our work from the fabrication and development of a novel microfluidic-based chip (PeptiCHIP) and to its use to identify and characterize tumor-speficic ligands on clinically relevant human organoids. Specifically, we assessed the potential of immobilizing a pan-HLA antibody on solid surfaces via well-characterized streptavidin-biotin chemistry, overcoming the limitations of the cross-linking chemistry used to prepare the affinity matrix with the desired antibodies in the immunopeptidomics workflow. Furthermore, to address the restrictions related to the handling and the limited availability of tumour samples, we further developed the concept towards the implementation of a microfluidic through-flow system. Thus, the biotinylated pan-HLA antibody was immobilized on streptavidin-functionalized surfaces, and immune-affinity purification (IP) was carried out on customized microfluidic pillar arrays made of thiol-ene polymer. Compared to the standard methods reported in the field, our methodology drastically reduces the handling, the amount of antibody and the time required for peptide isolation. In this work, we carefully examined the specificity and robustness of our customized technology for immunopeptidomics workflows. We tested this novel platform by immunopurifying HLA-I complexes from as few as 106 cells both in a widely studied B-cell line and in patients-derived ex vivo cell cultures. After the final elution in mild acid, HLA-I-presented peptides were identified by tandem mass spectrometry and further investigated by in vitro methods. These results highlight the potential to exploit microfluidics-based strategies in immunopeptidomics platforms and in personalized immunopeptidome analysis from cells isolated from individual tumour biopsies to design tailored cancer therapeutic vaccines.

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“…However, the tumor point mutations complexity poses limitations for the identification of a neoepitope that will elicit an effective immune response. This subject was recently reviewed in [124,125].…”

Section: Tumor Vaccinesmentioning

confidence: 99%

Gene Therapy in Cancer Treatment: Why Go Nano?

et al. 2020

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The proposal of gene therapy to tackle cancer development has been instrumental for the development of novel approaches and strategies to fight this disease, but the efficacy of the proposed strategies has still fallen short of delivering the full potential of gene therapy in the clinic. Despite the plethora of gene modulation approaches, e.g., gene silencing, antisense therapy, RNA interference, gene and genome editing, finding a way to efficiently deliver these effectors to the desired cell and tissue has been a challenge. Nanomedicine has put forward several innovative platforms to overcome this obstacle. Most of these platforms rely on the application of nanoscale structures, with particular focus on nanoparticles. Herein, we review the current trends on the use of nanoparticles designed for cancer gene therapy, including inorganic, organic, or biological (e.g., exosomes) variants, in clinical development and their progress towards clinical applications.

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Prediction of cancer neoepitopes needs new rules

Cited by 23 publications

References 67 publications

An unbiased approach to defining bona fide cancer neoepitopes that elicit immune-mediated cancer rejection

An unbiased approach to defining bona fide cancer neoepitopes that elicit immune-mediated cancer rejection

PeptiCHIP: a novel microfluidic-based chip platform for tumour antigen landscape identification

Gene Therapy in Cancer Treatment: Why Go Nano?

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